Table 2.
Mean (range) pharmacokinetic parameters following a single dose of sucrose-formulated recombinant factor VIII (rFVIII-FS) and single and multiple doses of BAY 94-9027 (chromogenic assay)
| Dose (IU kg−1) | t½ (h) | Cmax (IU dL−1) | Cmax,norm (kg dL−1) | AUC (IU h−1 dL–1) | AUCnorm (kg h−1 dL–1) | CL (dL h−1 kg–1) | Vss (dL kg−1) | |
|---|---|---|---|---|---|---|---|---|
| Cohort 1 (n = 7) | ||||||||
| rFVIII-FS* | 25 | 12.9 (8.4–18.7) | 69.6 (40.8–91.3) | 2.8 (1.6–3.7) | 1109 (580–2136) | 44.3 (23.2–85.4) | 0.023 (0.012–0.043) | 0.42 (0.31–0.66) |
| BAY 94-9027, single dose | 25 | 18.2 (13.7–28.1) | 63.7 (53.2–80.3) | 2.5 (2.1–3.2) | 1577 (1285–2825) | 61.3 (51.1–113.0) | 0.016 (0.009–0.020) | 0.43 (0.35–0.50) |
| BAY 94-9027, twice weekly (16 doses) | 25 | 18.6 (12.1–30.0) | 79.8 (62.0–92.9) | 3.2 (2.5–3.7) | 2036 (1452–3314) | 81.4 (57.8–132.5) | 0.012 (0.008–0.017) | 0.33 (0.30–0.40) |
| Cohort 2 (n = 7) | ||||||||
| rFVIII-FS | 50 | 13.0 (10.2–15.9) | 228.6 (171–376) | 4.6 (3.4–7.5) | 2502 (1736–4891) | 50.0 (34.7–97.8) | 0.020 (0.010–0.029) | 0.36 (0.23–0.51) |
| BAY 94-9027, single dose | 60 | 18.5 (15.1–23.4) | 172.0 (125–245) | 2.9 (2.1–4.1) | 4329 (3087–8578) | 72.1 (51.4–143.0) | 0.014 (0.007–0.019) | 0.38 (0.25–0.45) |
| BAY 94-9027, once weekly (nine doses) | 60 | 19.5 (15.0–25.6) | 184.7 (139–243) | 3.1 (2.3–4.1) | 4723 (3306–7589) | 78.5 (55.2–126.5) | 0.013 (0.008–0.018) | 0.34 (0.26–0.41) |
AUC, area under the curve from time zero to infinity; AUCnorm, dose-normalized area under the curve from time zero to infinity; CL, clearance; Cmax, maximum concentration; Cmax,norm, dose-normalized maximum concentration; t½, half-life; Vss, volume of distribution at steady state.
*
n = 6, except for Cmax and Cmax,norm, which are based on n = 7.